Pharmacokinetics and pharmacodynamics of AQST-109 sublingual film in oral allergy syndrome: A phase 2 study.

BACKGROUND

AQST-109 is an investigational epinephrine prodrug sublingual film for anaphylaxis treatment, with well-characterized pharmacokinetics (PK) and pharmacodynamics (PD) in healthy adults. It is unclear how oral symptoms during allergic reactions may affect its absorption and these parameters.

OBJECTIVE

To compare AQST-109's PK and PD in adults with oral allergy syndrome undergoing oral allergen challenge (OAC) to elicit symptoms.

METHODS

This was a phase 2, 2-part, open-label, randomized, fixed-sequence, stratified, crossover study to evaluate the PK and PD of single (12 mg) and repeat doses (12 mg × 2) of AQST-109 in adults with screening-confirmed oral allergy syndrome administered with and without OAC, and of single (0.3 mg) and repeat doses (0.3 mg × 2) of manual intramuscular epinephrine injection given without OAC. Geometric means for PK and PD parameters were analyzed for the PK, PD, and safety subsets.

RESULTS

During screening with OAC, 94.4% of the 36 patients experienced moderate or severe oral symptoms. Pharmacodynamics were not impacted by OAC after single- and repeat-dose administration of AQST-109 vs without OAC. AQST-109 PK values were similar with or without OAC. Single- and repeat-dosing PD parameters were higher with AQST-109 after OAC vs intramuscular epinephrine injection without OAC, and were nonsignificantly higher for AQST-109 with vs without OAC. Almost all patients experienced a related mild treatment-emergent adverse event; 4 were considered moderate in severity, and no new safety signals were identified compared with previous studies.

CONCLUSION

AQST-109 PK and PD are not diminished with oral symptoms and changes, supporting reliable absorption in allergic reactions in such contexts.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06527937.